Many chemotherapeutic agents, for example, antimetabolites (methotrexate, 5-fluoouracil, cytarabine), alkylating agents (cyclophosphamide, mechlorethamine, dacarbazine, ifosfamide), antineoplatic antibiotics (bleomycin, actinomycin D, daunomycin, doxorubicin, mitoxantrone), the vinca alkaloids (vincistine, vinblastine) and taxanes (Taxol, Taxotere), produce an anagen effluvium to induce alopecia by killing the active proliferating cells of the hair matrix. Scalp hair is particularly sensitive since 85% of scalp hair is in anagen phase. Chemotherapy-induced alopecia (CIA) is thus a major problem in clinical oncology, which can be a major obstacle for patients to accept chemotherapy. It is particularly devastating to women as alopecia-inducing agents such as the taxanes are becoming more frequently used in breast and ovarian cancers.
Surgical transplantation of small, discrete, skin areas having viable follicles to areas having inactive follicles is expensive, labor-intensive and relatively short-lasting. Also, as described by R. F. Oliver et al. in U.S. Pat. No. 4,919,664, follicular dermal cells can be inserted into a skin incision, resulting in hair growth along the incision. However, this is a complex technique that does nothing to stimulate existing follicles. Treatment of the hair and skin with various creams or lotions with biologically active ingredients to improve hair growth has generally low efficiency. Attempts to follow this approach have been ineffective, possibly because of the inability of stimulators to penetrate the cellular membrane of hair follicle cells and to enter into the cells where their action is needed.
Liposomes, which are artificial phospholipid vesicles, have been successfully used for delivery of different low-molecular-weight water-soluble and oil-soluble compounds into different cells. See, for example, G. Gregoriadis, Trends in Biotechnology (1985) 3:235-241 and K. H. Schmidt, ed., Liposomes as Drug Carriers, Stuttgart:George Thieme Verlag (1986). The applications and issued patents from which priority is claimed describe the use of liposomes to target hair follicles specifically.
No pharmacological agent inhibits CIA in a reliable, cost-efficient, unharmful and long-lasting manner. The treatment of human hair loss, especially CIA is important and beneficial for cancer patients and other persons generally. Thus, new agents and treatments for the prevention of CIA are needed.
It has been verified, as exemplified below, that chemotherapy-induced alopecia can be almost completely prevented in skin histoculture by liposome targeting of the gene encoding the cyclin-dependent-kinase inhibitor p21 to the hair follicle.